Phages are bacterial viruses. For example, lambda phage encapsulates a 48.5 kD duplex DNA in a capsid head of about 55 nm diameter. The genetics of lambda phage are well established and well understood. For example, the lambda D protein is a small protein (11.4 kDa) that acts to stabilize the lambda phage head or capsid but is dispensable for heads packaged with a DNA duplex less than 82% of the wild type lambda genome. As is well known to those of skill in the art, versions of lambda can be used as insertion or replacement vectors for cloning foreign DNA up to about 24 kilobase pairs (kbp).
Phages (in general), when administered to an animal rapidly circulate throughout the tissues of the animal and are removed from the circulation by the spleen, liver and filtering organs of the reticuloendothelial system (Geier et al., 1973, Nature 246: 221-223; Inchley, Clin Exp Immunol 5: 173-187; Keller and Engley, 1958, Proc Soc Exp Biol Med 98: 577-580). Phages have maintained viability for up to 2-3 weeks in spleen cells, indicating that they were neither neutralized by antibody nor engulfed by macrophages, but rather passively entrapped (sequestered). Viable phages have been detected in the circulation within 5 minutes of gastric delivery in mice, suggesting that significant numbers of phages can enter the circulation by diffusion, rather than via the lymphatic system (Keller and Engley, 1958). Phages delivered orally to rabbits were found in the blood plasma and most organs up to 4 days after administration, and persisted in the blood plasma and most organs up to 4 days after administration, and persisted in the spleen up to 12 days (Reynaud et al., 1992, Vet Microbiol 30: 203-212).